This project is exploring the antitumor capacity of different classes of mononuclear leukocytes in the mouse, assessed in vitro. Recent efforts have concentrated on two models in which peritoneal macrophages (rather than adherent peritoneal lymphoid cells) appear to be potent effectors. In both models, macrophages are cytotoxic only after activation, such as by treatment of the cell donors with Bacille Calmette-Guerin or C. parvum. In the first model, tumor cells are lysed only if the macrophages are triggered pharmacologically, by phorbol myristate acetate. In the second model, tumor cells are lysed only if the macrophages are triggered immunologically, by antiserum directed against the tumor cells. The biochemical basis of cytotoxicity has been elucidated in the first model. Activated macrophages and granulocytes, when triggered by suitable pharmacologic agents, release hydrogen peroxide. The hydrogen peroxide mediates target cell destruction. The role of oxidative metabolism in the second model is under study.